Virtual screening is an in silico approach method capable of rapidly anticipating the binding of a molecule from a compound library to a target receptor and effectively prioritizing molecules with related biological activities for further validation experiments. In order to overcome a high cost problem of the disadvantage of an experimental high-throughput screening (HTS) method, a large amount of compound library requires selective downsizing into a small set that can include a specific target drug. To this end, virtual screening has been increasingly applied in drug discovery projects prior to the experimental HTS. The application of various virtual screening techniques can significantly increase the efficiency of research in the field of drug discovery. One of the widely applied techniques in virtual screening is to compare two-dimensional (2D) properties between the experimentally determined ligands and the molecules of a compound library. In this approach method, the structural characteristics of molecules are expressed by the kind of constituent atoms and their bond levels. Another technique is to use the three-dimensional structural properties of molecules to compare similarities between molecules. Three-dimensional structure-based virtual screening approach methods are classified mainly into an approach method based on ligand coordinates and an approach method based on receptor coordinates. Like a two-dimensional (2D) method, the ligand-based approach method searches for molecules similar to the experimentally determined active ligand by comparing the three-dimensional structure properties between the molecules. This approach method is typically applied where only limited information about a target receptor is available. The ligand-based method essentially includes a comparative analysis process of structural properties, and accordingly, the application thereof necessarily requires information acquisition of the known active ligand. One of the available programs, Rapid Overlay of Chemical Structures (ROCS), uses an overlapping method for large form-based comparisons. ROCS adopts a method of comparing the structural similarities between two molecules based on the three-dimensional form. The three-dimensional form of the parameterized specifically expressed molecule uses Gaussian-based overlap to obtain the optimal alignment of the largest volume overlapping between two molecules. Since the similarity of chemical properties as well as the morphological similarity of molecules is a crucial factor in biological activity, the overlap between the functional groups that a compound has is additionally calculated using a color force field. The conformational flexibility of molecules can be considered by precomputing conformers ensembles in advance and sequentially comparing each of them. The excellence of the ROCS method has been reported through a number of research literature. When high-resolution coordinates of a target receptor are available, molecular docking is a common method of selection in virtual screening. Docking is used to quantify the binding affinity between molecules and receptors from a compound library by computer operation and to predict the binding potential between them. In essence, this method does not necessarily require information about a compound that is active for a drug target, but it can increase performance by incorporating the binding properties of a known active material into a docking process.
An antagonist, on the other hand, is a substance that binds to a receptor of a certain agonist but does not exhibit the physiological action through the receptor. TLR2 (Toll-like receptor 2) is present in the plasma membrane or endosome and belongs to the first line of defense of host defense in the inflammatory response. Signaling associated with TLR2 has been reported to have an association with cancer, tuberculosis, anemia, atopic dermatitis, and atherosclerosis. In particular, antagonists of TLR2 have become a major pharmacological target due to its inhibitory effect on inflammatory diseases. Accordingly, there is a need to screen for antagonists of novel TRL2 that can be used pharmacologically. In particular, research for screening antagonists that are small molecules is needed.